¿De vuelta a Los ocho años? A propósito de La guerra de Figueres, de Guillermo Villegas Hoffmaister

El libro de Guillermo Villegas Hoffmeister, “La guerra de Figueres”, tiene sin duda el subtítulo exacto Crónica de ocho años, porque eso es lo que es. Basado en alguna documentación escrita, en sus propios recuerdos personales y en una revisión de los periodos de la década de 1940, la obra se presenta ante todo como un producto de entrevistas realizadas por el autor a distintos personajes de la época. El resultado final es una narrativa descriptiva y parcializada, que combina alguna información interesante con datos sin importancia y algunas notables inexactitudes históricas: por ejemplo, el autor afirma que ¡el partido republicano nacional fue fundado por Maximiliano Fernández en 1909!, y en lo que parece ser producto de un lamentable descuido de él y de la EUNED, fecha la batalla de tejar el 13 de marzo en vez del 13 de abril de 1948…UCR::Vicerrectoría de Investigación::Unidades de Investigación::Artes y Letras::Centro de Investigación en Identidad y Cultura Latinoamérica (CIICLA

Attenuation of Progressive Hearing Loss in DBA/2J Mice by Reagents that Affect Epigenetic Modifications Is Associated with Up-Regulation of the Zinc Importer Zip4

<div><p>Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, <i>Zip4</i>, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the <i>Zip4</i> inducer (–)-epigallocatechin-3-<i>O</i>-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of <i>Zip4</i> expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.</p></div

The top 20 significantly up- or down-regulated genes in the M+V-treated cochleae relative to control vehicle-treated cochleae.

<p>*M+V, l-methionine and valproic acid; ctrl, vehicle control.</p><p>**Genes in bold were validated by qRT-PCR.</p><p>The top 20 significantly up- or down-regulated genes in the M+V-treated cochleae relative to control vehicle-treated cochleae.</p

Effect of EGCG treatment on progressive hearing loss in DBA mice.

<p>(A) ABR threshold increases at 8, 16, and 32 kHz in DBA mice treated with different doses of EGCG; N = 5 untreated (unt) mice, 5 saline-treated mice, 6 EG5 mice, and 5 EG10 mice. (B) Expression levels of <i>Zip4</i> in the whole cochleae from mice treated with EGCG and from untreated and saline-treated mice. N = 3 mice per group. Values shown are the mean ± s.d.; *<i>p</i> < 0.05, **<i>p</i> <0.01 (one-way ANOVA and Scheffe’s test).</p

Effects of reagents that affect epigenetic modification on progressive hearing loss in DBA mice.

<p>ABR threshold increases at 8, 16, and 32 kHz in DBA mice from 4 to 12 weeks of age that were treated with different reagents. Values shown are the mean ± s.d.; *<i>p</i> < 0.05, **<i>p</i> <0.01 (one-way ANOVA and Scheffe’s test). The numbers of animals in each group were as follows: 5 for untreated (unt), 19 for control (ctrl), 21 for M+V, 10 each for MET and VPA, and 11 each for FA and VB12. SPL, sound pressure level.</p

Additional file 3: of Mitochondrial mutations in maternally inherited hearing loss

Clinical features of probands carrying m.1555A > G or m.3243A > G. (XLSX 11 kb

The top 20 significantly up- or down-regulated genes in the M+V-treated cochleae relative to control vehicle-treated cochleae.

<p>*M+V, l-methionine and valproic acid; ctrl, vehicle control.</p><p>**Genes in bold were validated by qRT-PCR.</p><p>The top 20 significantly up- or down-regulated genes in the M+V-treated cochleae relative to control vehicle-treated cochleae.</p

Expression of <i>Zip4</i> in the cochlea of DBA mice.

<p><i>Zip4/Gapdh</i> ratios in the left whole cochleae of DBA mice at 4 weeks of age (4w) and in untreated cochleae (unt) and cochleae treated with vehicle control (ctrl) or with M+V from DBA mice at 12 weeks of age. N = 3 mice. Values shown are the mean ± s.d.; *<i>p</i> < 0.05, **<i>p</i> <0.01 (one-way ANOVA and Scheffe’s test).</p

Distribution of Zip4 in the cochlea of DBA mice.

<p>Cochlear specimens from 4-week-old (4w; A, B) and untreated (unt) 12-week-old (C, D) mice and from 12-week-old mice treated with vehicle control (ctrl; E, F) or with M+V (G, H) were incubated with rabbit antiserum against Zip4 (green) and monoclonal antibody against tubulin βIII (red). A, C, E, and G are dark-field images of B, D, F, and H, respectively. Scale bar = 100 μm. idc, interdental cell region; OC, organ of Corti; SG, spiral ganglion; SLg, spiral ligament; SLm, spiral limbus; StV, stria vascularis.</p

<i>Dnmt</i>s and <i>Hdac</i>s in the developing mouse auditory epithelium.

<p>(A) Expression levels of <i>Dnmt</i>s in the auditory epithelia of FVB mice at P1, P14, and 12 weeks (12w). Values shown are the mean ± s.d.; *<i>p</i> < 0.05, **<i>p</i> < 0.01 (N = 3 mice, one-way ANOVA and Scheffe’s test). (B) Expression of <i>Hdac</i>s in the developing auditory epithelia of FVB mice as assessed with RT-PCR.</p